scholarly journals Loss of ARID1A Expression as a Favorable Prognostic Factor in Early-Stage Grade 3 Endometrioid Endometrial Carcinoma Patients

2021 ◽  
Vol 27 ◽  
Author(s):  
Mayumi Kobayashi Kato ◽  
Hiroshi Yoshida ◽  
Yasuhito Tanase ◽  
Masaya Uno ◽  
Mitsuya Ishikawa ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Endometrial Carcinoma ◽  
Early Stage ◽  
Rank Test ◽  
Prognostic Impact ◽  
Protein Expressions ◽  
Impact On Survival ◽  
Endometrioid Endometrial Carcinoma ◽  
Grade 3 ◽  
Expression Status

Introduction: High-risk patients with grade 3 endometrioid endometrial carcinoma (G3EEC) who require adjuvant therapy have not been clearly identified. Therefore, the current study aimed to investigate the prognostic impact of ARID1A, p53, and mismatch repair (MMR) protein expressions, previously reported as prognosticators in some gynecological cancers, in patients with early-stage G3EEC.Methods: A total of 67 patients with pathologically confirmed early-stage G3EEC diagnosed between 1997 and 2020 were identified; none received adjuvant chemotherapy. The recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared with a log-rank test. The protein expressions of ARID1A, p53, and MMR were examined via immunohistochemistry, and the associations between these biomarkers and clinical outcomes were evaluated.Results: Recurrence was observed in 9 (13%) of the 67 patients with early stage G3EEC. The respective 5-years RFS and OS rates were 87.7% and 93.7%, and 68.6% and 85.7%, respectively for stages I and II. Multivariate analysis showed significantly longer RFS among patients with ARID1A loss (hazard ratio = 8.7; 95% CI, 1.09–69.6, p = 0.04). No significant differences were observed in RFS and OS of patients according to p53 and MMR expression status.Conclusion: ARID1A expression status was a prognosticator for patients with early stage G3EEC without adjuvant therapy, whereas p53 and MMR expression status showed no impact on survival outcomes. ARID1A may become a useful biomarker for stratification of adjuvant treatment for early stage G3EEC patients.

Undifferentiated endometrial carcinoma: a National Cancer Database analysis of prognostic factors and treatment outcomes

2019 ◽  
Vol 29 (7) ◽  
pp. 1126-1133
Author(s):  
Mariam AlHilli ◽  
Paul Elson ◽  
Lisa Rybicki ◽  
Sudha Amarnath ◽  
Bin Yang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Adjuvant Therapy ◽  
Endometrial Carcinoma ◽  
Treatment Outcomes ◽  
Survival Data ◽  
Early Stage ◽  
National Cancer Database ◽  
Early Stage Disease ◽  
Prognostic Groups

BackgroundUndifferentiated endometrioid endometrial carcinoma of the uterus is a rare, highly aggressive, and under-recognized subtype of endometrial cancer.ObjectiveThis study evaluates survival, prognostic factors for survival, and treatment outcomes associated with undifferentiated endometrial cancer.MethodsThe National Cancer Database was queried to identify patients with undifferentiated endometrial cancer who underwent definitive primary surgical treatment. Patients with all other histologic subtypes or incomplete treatment data were excluded. Univariable and multivariable Cox proportional hazards analyses were used to determine independent prognostic factors for survival. Points for each prognostic factor were assigned from regression coefficients in the final multivariable model and summed for a total score. Recursive partitioning analysis was used to determine cut-offs in the score to identify unique prognostic groups.ResultsAmong 349 404 women diagnosed with endometrial cancer from 2004 to 2013, 3994 (1.1%) met the criteria for diagnosis of undifferentiated endometrial cancer and 3486 had survival data. Median age at diagnosis was 65 years (interquartile range (IQR) 57–74) and 58% of patients had early stage disease. Median interval from diagnosis to surgery was 3.7 weeks (IQR 2.0–5.7). Five year overall survival was 57% (standard error (SE) 1%). Stage was the strongest predictor of survival, with a 15–20% decrement in 5 year survival for each advance in stage. Stage, age, race, and presence of comorbidities were independent predictors of survival and were used to categorize patients into five prognostic groups. Adjuvant therapy was associated with improved survival across most disease stages and prognostic groups. Multimodal adjuvant therapy was superior to unimodal treatment particularly in advanced stage unfavorable and very unfavorable groups.ConclusionIn women with undifferentiated endometrial cancer, survival is primarily driven by stage. Despite the poor overall prognosis of undifferentiated endometrial cancer, multimodal adjuvant therapy is a key component of treatment.

Intra-Follicular Proliferation Rate Is a Powerful Independent Prognosticator in Follicular Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4571-4571
Author(s):  
Ad Koster ◽  
Hedwig A. Tromp ◽  
John M. Raemaekers ◽  
George F. Borm ◽  
Marius A. MacKenzie ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Univariate Analysis ◽  
Proliferation Rate ◽  
Rank Test ◽  
Low Grade ◽  
Prognostic Impact ◽  
Bulky Disease ◽  
Histologic Grading ◽  
Grade 3 ◽  
Mib 1

Abstract Several prognostic scores are used to predict the outcome of patients with follicular lymphoma (FL). Histologic grading is widely used, but poorly reproducible. Scoring systems such as the (FL)IPI consist of surrogate clinical markers that probably reflect underlying biological phenomena. We hypothesized that the proliferation rate of the intra-follicular neoplastic cells in FL may predict clinical outcome. Proliferating cells were identified by using the Mib-1 antibody in pre-treatment lymph node biopsies of 51 patients. In each section 200 cells per follicle were assessed in five follicles. The proliferation ratio (PR) was defined as (no. of Mib-1 positive cells/ total no. of cells) x 100. The PR was assessed only in the follicles, since many proliferating, non-malignant cells are present in the inter-follicular area. The inter-observer variability was assessed by repeating this procedure for 25 cases by a second investigator blinded to the outcome of the first assessment, resulting in a correlation coefficient of 0.81 (p < 0.001). All patients participated in a prospective multicenter trial on first-line treatment with the combination of 8 cycles of CVP (cyclophosphamide, vincristine and prednisone) chemotherapy plus interferon-alpha2b, followed by interferon-alpha maintenance in responding patients until relapse or progression. For statistical analysis the Kaplan-Meier product limit method, the log-rank test, the Cox proportional hazard model and the Mann-Whitney-U test were used. The median age of the patients was 53.3 years; 37 patients had stage IV disease; in nine patients a wait and see interval preceded the treatment (median duration 13 months). A low IPI score was present in 27 patients, intermediate in 20 and high in one. (three patients unknown). After central revision of the original diagnosis six patients were classified as grade 3 FL, 45 as grade 1 or 2. The overall median PR was 16.9 (3.1–49.2). In grade 1 and 2 FL the median PR was 16.1, in grade 3 it was 24.2 (p = 0.02). After a median follow-up of 71 months the median progression-free survival (PFS) for all patients was 25 months. The median PFS was not reached in the patients with the PR below the median compared to only 15 months in the patients with the PR above the median (p = 0.00059). In patients with the PR below median, overall survival was not reached compared to only 42 months in patients with a high PR (p = 0.0019). The PR maintained its prognostic impact on PFS and OS when tested as a continuous variable (p = 0.016 and 0.053 resp.). When the six patients with grade 3 FL were excluded from the analysis, the results remained significant. Other parameters that were significantly associated with a worse OS in univariate analysis were male sex, the presence of bulky disease and intermediate or high IPI. In multivariate analysis the association of high PR with a worse OS remained significant. We found that in FL intra-follicular proliferation rate is a strong independent prognostic factor of PFS and OS. Grade 3 FL appeared to have a higher PR than low grade FL, although numbers are small in this study. PR assessment is easy, relatively fast and reproducible. When confirmed in larger series, the intra-follicular PR could be used instead of histologic grading in identifying the aggressive types of follicular lymphoma, requiring other types of treatment.

scholarly journals Analysis of recurrence and survival rates in grade 3 endometrioid endometrial carcinoma

2016 ◽  
Vol 12 (4) ◽  
pp. 2860-2867 ◽  
Author(s):  
Jieyu Wang ◽  
Nan Jia ◽  
Qing Li ◽  
Chao Wang ◽  
Xiang Tao ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Survival Rates ◽  
Endometrioid Endometrial Carcinoma ◽  
Grade 3

scholarly journals Disease-Specific Survival of Type I and Type II Epithelial Ovarian Cancers—Stage Challenges Categorical Assignments of Indolence & Aggressiveness

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 56
Author(s):  
Edward J. Pavlik ◽  
Christopher Smith ◽  
Taylor S. Dennis ◽  
Elizabeth Harvey ◽  
Bin Huang ◽  
...  
Keyword(s):  
Late Stage ◽  
Early Stage ◽  
Rank Test ◽  
Type I ◽  
Type Ii ◽  
Disease Specific Survival ◽  
Ovarian Cancers ◽  
Seer Data ◽  
Grade 3 ◽  
Disease Specific

Epithelial ovarian cancers (EOC) consist of several sub-types based on histology, clinical, molecular and epidemiological features that are termed “histo-types”, which can be categorized into less aggressive Type I and more aggressive Type II malignancies. This investigation evaluated the disease-specific survival (DSS) of women with Type I and II EOC using histo-type, grade, and stage. A total of 47,789 EOC cases were identified in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) data. Survival analysis and log rank test were performed to identify a 2-tiered classification (grade 1 vs. grade 2 & 3) for serous EOC. DSS of early stage serous EOC for grade 2 was significantly different from grade 3 indicating that a 2-tier classification for serous EOC applied only to late stage. DSS of Type I EOC was much better than Type II. However, DSS was 33–52% lower with late stage Type I than with early stage Type I indicating that Type I ovarian cancers should not be considered indolent. Early stage Type II EOC had much better DSS than late stage Type II stressing that stage has a large role in survival of both Type I and II EOC.

scholarly journals Complete Clinical Response in Stage IVB Endometrioid Endometrial Carcinoma after First-Line Pembrolizumab Therapy: Report of a Case with Isolated Loss of PMS2 Protein

2020 ◽  
Vol 13 (3) ◽  
pp. 1067-1074
Author(s):  
Jesus Paula Carvalho ◽  
Auro Del Giglio ◽  
Maria Isabel Achatz ◽  
Filomena Marino Carvalho
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Endometrial Carcinoma ◽  
Early Stage ◽  
Gynecological Cancer ◽  
Stage Iv ◽  
Protein Loss ◽  
First Line ◽  
Early Stage Disease ◽  
Endometrioid Endometrial Carcinoma

Endometrial cancer is the only gynecological cancer that is rising in incidence and associated mortality worldwide. Although most cases are diagnosed as early stage disease, with chances of cure after primary surgical treatment, those with advanced or metastatic disease have a poor prognosis because of the quality of treatment options that are currently available. Mismatch repair (MMR)-deficient cancers are susceptible to programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 inhibitors. The US Food and Drug Administration granted accelerated approval to pembrolizumab for MMR-deficient tumors, the first tumor-agnostic approval for a drug. We present a case of stage IV endometrioid endometrial carcinoma with isolated PMS2 protein loss, in which treatment with first-line pembrolizumab therapy achieved a complete clinical and pathological response of tumor.

Present-day management of uterine leiomyosarcoma: Evaluation of treatment sequencing and other prognostic factors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18035-e18035
Author(s):  
Emily Hinchcliff ◽  
Jennifer Rumpf ◽  
Ravin Ratan ◽  
Nicole D. Fleming ◽  
Amir A. Jazaeri ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Early Stage ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Molecular Testing ◽  
Common Mutation ◽  
Uterine Leiomyosarcoma ◽  
Free Survival ◽  
Er Positive ◽  
Grade 3

e18035 Background: Uterine leiomyosarcoma (ULMS) is a rare tumor with limited therapeutic options and no clearly established best treatment sequence strategy. Methods: Women with ULMS between 2013-2018 were identified. Clinical data was collected; descriptive statistics were performed and predictors of overall survival (OS) and progression free survival (PFS) were analyzed. Results: 189 patients were included. Median age was 53 (20-84), 91% had grade 3 tumors and 51.3% had stage IB disease. 50% underwent surgery followed by chemotherapy (n = 94, 49.7%) and 37% had surgery only (n = 70). 49 patients retained their ovaries; there was no difference in OS by oophorectomy status (p = 0.71). Estrogen and progesterone receptor (ER/PR) status, positive in 41% and 33% respectively, was not independently associated with OS (p = 0.23, p = 0.12) nor did it impact OS among those with oophorectomy and without (p = 0.70). The most common adjuvant therapy regimens were gemcitabine/docetaxel (gem/doce, 64%) or ifosphamide/doxorubicin (ifos/doxo, 19%). There were no differences in the regimens prescribed by physician specialty (gynecologic oncology vs other, p = 0.21). 147 patients (78%) experienced a recurrence or progression. For the 73 patients who received gem/doce as adjuvant therapy, 58.9% recurred and were most commonly treated with doxo containing regimens (67%). Of the 22 patients treated with ifos/doxo, only 3 recurred and each received a different second line regimen. For those not treated with adjuvant therapy (70 patients), 58.2% recurred and were treated with gem/doce (62%) and ifos/doxo (24%). In early stage patients, the majority received surgery only (45%) or surgery followed by chemotherapy (44%). There was no difference in OS in those who received adjuvant therapy and those who did not (p = 0.39). 46 (24%) had molecular testing and 37 had identified mutations. The most common mutation found was P53 (n = 25, 54%) followed by RB1 (8, 17%), PTEN (7, 15%), and BRCA (2, 4%). Conclusions: Recurrence occurred in 78% of patient despite many women undergoing adjuvant therapy after surgery. Oophorectomy did not influence OS, even though 41% of tumors were ER positive. The sequence of treatment was not associated with OS, however, the risk for recurrence in patient treated with adjuvant Ifos/Doxo was 14% compared to 59% in gem/doce. This finding warrants additional evaluation to determine the optimal adjuvant therapy for these women.

scholarly journals Tumor progression, metastasis, and modulators of epithelial–mesenchymal transition in endometrioid endometrial carcinoma: an update

2015 ◽  
Vol 23 (2) ◽  
pp. R85-R111 ◽  
Author(s):  
Annu Makker ◽  
Madhu Mati Goel
Keyword(s):  
High Risk ◽  
Tumor Progression ◽  
Endometrial Carcinoma ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Current Knowledge ◽  
Early Stage ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Endometrioid Endometrial Carcinoma

Endometrioid endometrial carcinoma (EEC), also known as type 1 endometrial cancer (EC), accounts for over 70–80% of all cases that are usually associated with estrogen stimulation and often develops in a background of atypical endometrial hyperplasia. The increased incidence of EC is mainly confined to this type of cancer. Most EEC patients present at an early stage and generally have a favorable prognosis; however, up to 30% of EEC present as high risk tumors, which have invaded deep into the myometrium at diagnosis and progressively lead to local or extra pelvic metastasis. The poor survival of advanced EC is related to the lack of effective therapies, which can be attributed to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis. Multiple lines of evidence illustrate that epithelial–mesenchymal transition (EMT)-like events are central to tumor progression and malignant transformation, endowing the incipient cancer cell with invasive and metastatic properties. The aim of this review is to summarize the current knowledge on molecular events associated with EMT in progression, invasion, and metastasis of EEC. Further, the role of epigenetic modifications and microRNA regulation, tumor microenvironment, and microcystic elongated and fragmented glands like invasion pattern have been discussed. We believe this article may perhaps stimulate further research in this field that may aid in identifying high risk patients within this clinically challenging patient group and also lead to the recognition of novel targets for the prevention of metastasis – the most fatal consequence of endometrial carcinogenesis.

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